EFFECTS OF FRUCTOSE-1,6-BISPHOSPHATE ON GLUTAMATE RELEASE AND ATP LOSS FROM RAT-BRAIN SLICES DURING HYPOXIA

Fructose-1,6-bisphosphate (FBP), an intermediate of glucose metabolism , is neuroprotective in brain hypoxia or ischemia. Because the mechani sms for this protection are not clear, we examined the effects of FBP on two important events in brain ischemia, i.e., loss of ATP and relea se of the excitatory neurotransmitter glutamate. Glutamate release fro m cortical brain slices was measured fluorometrically (glutamate dehyd rogenase-catalyzed conversion of glutamate to cu-ketoglutarate) during hypoxia (PO2 15 mm Hg) or hypoxia plus 100 mu M cyanide. FBP (3.5 mM, with glucose 20 mM) reduced glutamate release during hypoxia by 55% a nd during hypoxia/cyanide by 46% (p < 0.005), and prevented a signific ant fall in [ATP]. [ATP] was maintained in oxygenated glucose-free con ditions with 20 but not 3.5 mM FBP, and fell to <20% of normal with hy poxia. Despite the drop in [ATP], 3.5 or 20 mM FBP without glucose dec reased hypoxia-evoked glutamate release. We conclude (1) FBP present w ithout glucose preserves normal [ATP] only when oxygen is available, s uggesting limited uptake and metabolism; and (2) FBP decreases hypoxia -evoked glutamate release by processes independent of [ATP]. These res ults suggest protective actions of FBP that are separate from augmenta tion of anaerobic energy production, as previously proposed.